University of Massachusetts Medical School Faculty Publications
Title
Gene therapy for Canavan's disease takes a step forward
UMMS Affiliation
Gene Therapy Center; Department of Microbiology and Physiological Systems
Publication Date
2013-3
Document Type
Response or Comment
Subjects
Genetic Therapy; Canavan Disease
Disciplines
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Molecular Genetics | Nervous System | Nervous System Diseases | Nutritional and Metabolic Diseases | Therapeutics
Abstract
Canavan's disease (CD) is a rare but devastating pediatric leukodystrophy that causes progressive spongy neurodegeneration and is invariably fatal in congenital form.1 The disease is associated with >54 loss-of-function mutations2,3,4 in the enzyme aspartoacylase (ASPA), leads to accumulation of the substrate N-acetyl aspartic acid (NAA) in the brain, and is diagnosed via the presence of NAA aciduria.1 CD is characterized by dysmyelination, intramyelinic edema (leading to hydrocephalus), and extensive vacuolation of the central nervous system (CNS) white matter.5 Currently there is no established therapy that affects progression of the disease, and survival is based primarily on improved general medical care. A previous gene therapy attempt using liposome-encapsulated plasmid DNA6 had shown encouraging although transient decreases in local NAA concentrations in the treated brains, which prompted a gene therapy clinical protocol using recombinant AAV serotype 2 (rAAV2) in the hope of better dissemination of the vector and more sustainable NAA reductions.7 In a recent issue of Science Translational Medicine, Leone et al.8 report long-term follow-up of 13 of the 28 patients enrolled in this trial, who received intracranial injections of first-generation rAAV vectors-based on serotype 2 nearly a decade ago.
DOI of Published Version
10.1038/mt.2013.25
Source
Mol Ther. 2013 Mar;21(3):505-6. doi: 10.1038/mt.2013.25. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Molecular therapy : the journal of the American Society of Gene Therapy
PubMed ID
23449107
Repository Citation
Ahmed SS, Gao G. (2013). Gene therapy for Canavan's disease takes a step forward. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1038/mt.2013.25. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/170
Comments
First author Seemin Seher Ahmed is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.